| Project/Area Number |
17K10738
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Cardiovascular surgery
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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| Keywords | 心筋梗塞 / 線維芽細胞 / 細胞老化 / マクロファージ / 組織修復 / 心臓修復 |
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| Outline of Final Research Achievements |
We have recently reported that cardiac macrophages play the central role in cardiac repair post myocardial infarction (MI). However, the underpinning mechanism of this protective process is not fully understood. We hypothesized that reparative macrophages would protect fibroblasts from such damages and promote them to form fibrotic tissues. In the murine heart post-MI induced by coronary artery ligation, approximately one third of accumulated fibroblasts were apoptotic post-MI. Of note, this apoptosis was decreased when macrophages were further augmented by IL-4 administration. We further investigated this macrophage-mediated prevention of fibroblast damage in vitro. Hydrogen peroxide-induced apoptosis of cultured cardiac fibroblasts was markedly reduced by co-culture with bone marrow-derived macrophages. In conclusion, reparative macrophages protect cardiac fibroblasts from MI-related injury, which would support development of solid replacement fibrosis in the infarcted myocardium.
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| Academic Significance and Societal Importance of the Research Achievements |
近年心筋梗塞後の心不全患者は増加傾向で、心破裂による死亡率も極めて高いことから、心破裂・心不全の根本的な病因究明と新たな治療の確立が急務である。本研究の特色は、心筋梗塞発症後の心筋修復のメカニズムを掘り下げ、心破裂を予防するために十分な組織修復を誘導し、かつ心機能確保のための梗塞後の線維芽細胞を保護するための主要調節因子を特定することである。梗塞時のダメージを抑制することによるメリットが本研究で明らかになれば、長期的予後に対する新たな戦略に繋がる可能性がある。従って、本研究によって得られる研究成果は、心破裂予防・心不全予後の向上に重要な意義を有している。
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